The long range goal of this research is to gain insight into mechanisms underlying the modulation of synaptic transmission. It is now clear that many neurons contain more than one transmitter and it will be important to determine how multiple transmitters released from the terminals of single neurons interact on post- synaptic targets. Specifically, neuropeptides appear to commonly coexist along with conventional transmitters. The relatively simple nervous system of Aplysia has a number of advantages that make it particularly useful as a model system for these studies. One specific aim of this grant is to explore the hypothesis that neuropeptides which are present in motor neurons are released during stimulation to modulate the effectiveness of conventional excitatory transmitters such as acetylcholine released from the neuron. These neuropeptides have been shown to be potent modulators of neuromuscular transmission at these muscles. This will permit an evaluation of the role of corelease in food induced arousal, and extensively studied and well understood behavior in this animal. The characteristics of release of acetylcholine and these peptides will also be determined for identified neurons in primary culture. A second specific aim is to determine the physiological roles of a newly identified modulatory peptide that appears to be one of the major peptide transmitter in this animal. Understanding fundamental neural processes such as modulation of synaptic transmission at neuromuscular synapses could have relevance to disorders of movement as well as more general disorders of affect and cognition.